General CpG island questions - (Jun/29/2005 )

what is this CpG/GpC ratio that is usually refered to. What are the GpCs? and why is that ratio important?

QUOTE (methylnick @ Nov 27 2005, 01:44 AM)

Hi Hans, you have brought up some very valid questions.

QUOTE (hans @ Nov 26 2005, 11:42 PM)

So, do these methylated islands ocurr mostly in silenced genes? and I suppose they are much less common than unmethylated ones? and that all CpG islands associated with active genes are unmethylated?

methylated islands do occur at silenced genes, the best examples are from tumor suppressor genes in cancer, imprinted regions and of course genes found on the X-chromosome and subjected to X-inactivation.

QUOTE (hans @ Nov 26 2005, 11:42 PM)

I can see unmethylated CGIs associated with active genes, I dont know much about their association with Alus but I m happy sticking to Takai and Jones definition of CGI that exclude tose asssociated with Alus. But I dont know how is it that unmethylated CGIs are protected from methylation in GC rich regions. is it maybe similar to what protect CpG from deamination? (DNA melting; Fryxell and Moon 2005).

there are hypothesis existing that a demethylase enzyme actively maintains the CpG islands in a hypomethylated state. No one has yet characterised this yet. There are insulator elements such as CTCF and BORIS that bind to hypomethylated GC-rich regions and has been thought to sterically inhibit the methyltransferases from methylating the region.

I think that active transcription of the CpG I assocoiated genes have within the complex, proteins that are refractory to DNMT localisation and thus inhibits methylation.

The underlying question you have asked will be answered by the epigenome project found here. where every CpG site will be assayed for methylation. At the moment, the models presented by numerous groups are based on the best techniques available for global methylation studies employing methylation sensitive restriction enzymes, it is now becoming clear that MBD proteins are able to bind a single methylated CpG that does not necessarily have to reside in a CpG island, as MBDs are known to be associated with chromatin remodelling proteins and serve a function of maintaining a certain chromatin state, I feel that methylation certaiinly plays a role in chromatin maintenance with "side effects" of regulating gene expression.

Could you forward me the Fyyxel and moon citation? I am unable to find it through a pubmed search.

Cheers

Nick

-hans-

CpG to GpC ratio is slightly different to the usual calculation of the observed to expected ratio. Obs/exp is a number that is used to determine CpG frequency within a defined sequence. CpG islands also have a large grouping of CpG dinucleotides.

It is known that CpG dinucleotide frequency is five-fold less that what is expected should all dinucleotide combinations be of equal frequency of occurance. There are 16 possible combinations of dinucleotides and if all were equal this would mean a 1/16 expected frequency. Of course what is observed in a sequence is not always what is expected and for regions that are not CpG islands you would see this ratio well below 0.5. However at CpG islands, there are more CpG dinucleotides than expected and the ratio goes above 0.5. so I hope that explains it a bit more.

-methylnick-

Im sorry, but how do you come up with the expected ratio of 0.5?

QUOTE (methylnick @ Nov 27 2005, 05:37 PM)

CpG to GpC ratio is slightly different to the usual calculation of the observed to expected ratio. Obs/exp is a number that is used to determine CpG frequency within a defined sequence. CpG islands also have a large grouping of CpG dinucleotides.

It is known that CpG dinucleotide frequency is five-fold less that what is expected should all dinucleotide combinations be of equal frequency of occurance. There are 16 possible combinations of dinucleotides and if all were equal this would mean a 1/16 expected frequency. Of course what is observed in a sequence is not always what is expected and for regions that are not CpG islands you would see this ratio well below 0.5. However at CpG islands, there are more CpG dinucleotides than expected and the ratio goes above 0.5. so I hope that explains it a bit more.